1: FEBS J. 2005 Mar;272(5):1265-77. 

Identification and characterization of four novel peptide motifs that recognize
distinct regions of the transcription factor CP2.

Kang HC, Chung BM, Chae JH, Yang SI, Kim CG, Kim CG.

Department of Life Science, Hanyang University, Korea.

Although ubiquitously expressed, the transcriptional factor CP2 also exhibits
some tissue- or stage-specific activation toward certain genes such as globin in
red blood cells and interleukin-4 in T helper cells. Because this specificity
may be achieved by interaction with other proteins, we screened a peptide
display library and identified four consensus motifs in numerous CP2-binding
peptides: HXPR, PHL, ASR and PXHXH. Protein-database searching revealed that
RE-1 silencing factor (REST), Yin-Yang1 (YY1) and five other proteins have one
or two of these CP2-binding motifs. Glutathione S-transferase pull-down and
coimmunoprecipitation assays showed that two HXPR motif-containing proteins REST
and YY1 indeed were able to bind CP2. Importantly, this binding to CP2 was
almost abolished when a double amino acid substitution was made on the HXPR
sequence of REST and YY1 proteins. The suppressing effect of YY1 on CP2's
transcriptional activity was lost by this point mutation on the HXPR sequence of
YY1 and reduced by an HXPR-containing peptide, further supporting the
interaction between CP2 and YY1 via the HXPR sequence. Mapping the sites on CP2
for interaction with the four distinct CP2-binding motifs revealed at least
three different regions on CP2. This suggests that CP2 recognizes several
distinct binding motifs by virtue of employing different regions, thus being
able to interact with and regulate many cellular partners.

PMID: 15720400 [PubMed - indexed for MEDLINE]


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2: J Biomed Sci. 1995 Aug;2(3):203-226. 

Multiple Tandemly Repeated Binding Sites for the YY1 Repressor and Transcription
Factors AP-1 and SP-1 Are Clustered within Intron-1 of the Gene Encoding the
IE110 Transactivator of Herpes simplex Virus Type 1.

Gu W, Huang Q, Hayward GS.

Department of Pharmacology and Molecular Sciences, Johns Hopkins University
School of Medicine, Baltimore, Md., USA.

Expression of the IE110 (ICP0) transactivator protein of HSV appears to be
critical for reactivation from the latent state and occurs at immediate-early
times during the lytic cycle under the control of an upstream divergent
enhancer-promoter region that contains multiple Oct and Sp-1 binding sites
overlapping with VP16 response elements. Surprisingly, the large 800-bp first
intron of the HSV-1 IE110 gene also proved to have a complex repetitive
organization encompassing multiple transcription factor binding sites within
four distinct domains. DNaseI footprinting studies revealed that 13 of 17 copies
of a 15-bp repeated element represented high-affinity binding sites for the
cellular YY1 repressor protein. Between 4 and 7 of these sites are direct tandem
repeats and the rest are interpersed with three repeated AT-rich motifs and a
dyad symmetry region containing two strong AP-1 binding sites and an adjacent
SP-1 binding site on each arm. Several of the YY1 sites also bound weakly to
SRF. The intron also contains four clustered purine/pyrimidine tracts of between
16 and 23 bp long. Both the AP-1/AP-2/SP-1 dyad protein binding region and, to a
lesser extent, the YY1 tandem-repeat cluster conferred responsiveness to TPA
when placed upstream of a heterologous promoter in transient expression assays.
The functional significance of the HSV-1 IE110 intron region is unknown as yet,
but the novel arrangement of tandemly repeated YY1 sites has the potential to
produce structural bending and transcriptional attenuation effects.
Interestingly, few of these transcription factor binding motifs are conserved in
the equivalent IE110 intron of HSV-2, and the domain appears to represent a
unique alternative control region that is specific for HSV-1. Copyright 1995 S.
Karger AG, Basel

PMID: 11725057 [PubMed - as supplied by publisher]


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3: Biol Chem. 2001 Jun;382(6):891-902. 

Biological activity of mammalian transcriptional repressors.

Thiel G, Lietz M, Bach K, Guethlein L, Cibelli G.

Department of Medical Biochemistry and Molecular Biology, University of Saarland
Medical School, Homburg, Germany.

Research on the regulation of transcription in mammals has focused in recent
years mainly on the mechanism of transcriptional activation. However,
transcriptional repression mediated by repressor proteins is a common regulatory
mechanism in mammals and might play an important role in many biological
processes. To understand the molecular mechanism of transcriptional repression,
the activity of eight mammalian repressors or repressor domains was investigated
using a set of model promoters in combination with two different transcriptional
detection methods. The repressors studied were: REST, the thyroid hormone
receptors alpha and beta, the zinc finger protein NK10 containing a
'kruppel-associated box' (KRAB), repressor domains derived from the proteins
Egr-1, Oct2A and Dr1 and the repressor/activator protein YY1. Here we show that
the repressor domains of REST, Egr-1, the thyroid hormone receptors alpha< and
beta and NK10 were transferable to a heterologous DNA-binding domain and
repressed transcription from proximal and distal positions. Moreover, these
repressor domains also blocked the activity of a strong viral enhancer in a
'remote position'. Thus, these domains are 'general' transcriptional repressor
domains. The 'kruppel-associated box' was the most powerful repressor domain
tested. In contrast, the repressor domains derived from Oct2A and Dr1 were
inactive when fused to a heterologous DNA-binding domain. The repressor domain
of YY1 exhibited transcriptional repression activity only in one of the
transcriptional assay systems. The recruitment of histone deacetylases to the
proximity of the basal transcriptional apparatus was recently discussed as a
mechanism for some mammalian transcriptional repressor proteins. Here we show
here that histone deacetylase 2, targeted to the reporter gene via DNA-protein
interaction, functions as a transcriptional repressor protein regardless of the
location of its binding site within the transcription unit.

PMID: 11501753 [PubMed - indexed for MEDLINE]


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4: Prog Nucleic Acid Res Mol Biol. 1998;61:309-44. 

Structural organization and transcription regulation of nuclear genes encoding
the mammalian cytochrome c oxidase complex.

Lenka N, Vijayasarathy C, Mullick J, Avadhani NG.

Department of Animal Biology, School of Veterinary Medicine, University of
Pennsylvania, Philadelphia 19104, USA.

Cytochrome c Oxidase (COX) is the terminal component of the bacterial as well as
the mitochondrial respiratory chain complex that catalyzes the conversion of
redox energy to ATP. In eukaryotes, the oligomeric enzyme is bound to
mitochondrial innermembrane with subunits ranging from 7 to 13. Thus, its
biosynthesis involves a coordinate interplay between nuclear and mitochondrial
genomes. The largest subunits, I, II, and III, which represent the catalytic
core of the enzyme, are encoded by the mitochondrial DNA and are synthesized
within the mitochondria. The rest of the smaller subunits implicated in the
regulatory function are encoded on the nuclear DNA and imported into
mitochondria following their synthesis in the cytosol. Some of the nuclear coded
subunits are expressed in tissue and developmental specific isologs. The
ubiquitous subunits IV, Va, Vb, VIb, VIc, VIIb, VIIc, and VIII (L) are detected
in all the tissues, although the mRNA levels for the individual subunits vary in
different tissues. The tissue specific isologs VIa (H), VIIa (H), and VIII (H)
are exclusive to heart and skeletal muscle. cDNA sequence analysis of nuclear
coded subunits reveals 60 to 90% conservation among species both at the amino
acid and nucleotide level, with the exception of subunit VIII, which exhibits 40
to 80% interspecies homology. Functional genes for COX subunits IV, Vb, VIa 'L'
& 'H', VIIa 'L' & 'H', VIIc and VIII (H) from different mammalian species and
their 5' flanking putative promoter regions have been sequenced and extensively
characterized. The size of the genes range from 2 to 10 kb in length. Although
the number of introns and exons are identical between different species for a
given gene, the size varies across the species. A majority of COX genes
investigated, with the exception of muscle-specific COXVIII(H) gene, lack the
canonical 'TATAA' sequence and contain GC-rich sequences at the immediate
upstream region of transcription start site(s). In this respect, the promoter
structure of COX genes resemble those of many house-keeping genes. The
ubiquitous COX genes show extensive 5' heterogeneity with multiple transcription
initiation sites that bind to both general as well as specialized transcription
factors such as YY1 and GABP (NRF2/ets). The transcription activity of the
promoter in most of the ubiquitous genes is regulated by factors binding to the
5' upstream Sp1, NRF1, GABP (NRF2), and YY1 sites. Additionally, the murine
COXVb promoter contains a negative regulatory region that encompasses the
binding motifs with partial or full consensus to YY1, GTG, CArG, and ets.
Interestingly, the muscle-specific COX genes contain a number of striated
muscle-specific regulatory motifs such as E box, CArG, and MEF2 at the proximal
promoter regions. While the regulation of COXVIa (H) gene involves factors
binding to both MEF2 and E box in a skeletal muscle-specific fashion, the
COXVIII (H) gene is regulated by factors binding to two tandomly duplicated E
boxes in both skeletal and cardiac myocytes. The cardiac-specific factor has
been suggested to be a novel bHLH protein. Mammalian COX genes provide a
valuable system to study mechanisms of coordinated regulation of nuclear and
mitochondrial genes. The presence of conserved sequence motifs common to several
of the nuclear genes, which encode mitochondrial proteins, suggest a possible
regulatory function by common physiological factors like heme/O2/carbon source.
Thus, a well-orchestrated regulatory control and cross talks between the nuclear
and mitochondrial genomes in response to changes in the mitochondrial metabolic
conditions are key factors in the overall regulation of mitochondrial
biogenesis.

Publication Types:
    Review

PMID: 9752724 [PubMed - indexed for MEDLINE]


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